Potassium Hydroxide → HCID 66706900, compound

HRID 2041400Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20]C(=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].[Cl-].[NH4+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([SH:20])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

To 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (723 mg, 1.88 mmol) in methanol (10 mL) add potassium hydroxide pellets (3.34 g, 60.2 mmol) and stir mixture at 50° C. for 2 h. Cool to ambient temperature, add aqueous saturated ammonium chloride, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo to give the crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine. Dissolve the compound in DMF (5 mL), add cesium carbonate (920 mg, 2.82 mmol) and 1-bromomethyl-4-(3,3,3-trifluoro-2-methyl-2-trifluoromethyl-propane-1-sulfinyl)-benzene (824 mg, 2.071 mmol) and stir 2 h at ambient temperature. Dilute with water, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[4-(3,3,3-trifluoro-2-methyl-2-trifluoromethyl-propane-1-sulfinyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (986 mg, 83%). Use a method similar to the General Procedure 1-4 to give the title compound as a white foam. MS (ES+) m/z: 530 (M+H)+.

Workup

temperatureCool to ambient temperature
extractionextract three times with EtOAc
dry with materialdry over anhydrous Na2SO4
concentrationconcentrate in vacuo

Sources & evidence

ORD record: ord-f7b5952a6f7c40a891d3da82d44a5336
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

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